Modulation of tumor immune microenvironment by TAS-115, a multi-receptor tyrosine kinase inhibitor, promotes antitumor immunity and contributes anti-PD-1 antibody therapy.

ABSTRACT: TAS-115 is an oral multi-receptor tyrosine kinase inhibitor that strongly inhibits kinases implicated in antitumor immunity, such as colony stimulating factor 1 receptor and vascular endothelial growth factor receptor. Because these kinases are associated with the modulation of immune pathways, we investigated the immunomodulatory activity of TAS-115. An in vitro cytokine assay revealed that TAS-115 upregulated interferon γ (IFNγ) and interleukin-2 secretion by T cells, suggesting that TAS-115 activated T cells. Gene expression analysis suggested that TAS-115 promoted M1 macrophage differentiation. In in vivo experiments, although TAS-115 exerted a moderate antitumor effect in the MC38 mouse colorectal cancer model under immunodeficient conditions, this effect was enhanced under immunocomp

SUBMITTER: Shibutani T 

PROVIDER: S-EPMC10232527 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature